Sökning: id:"swepub:oai:DiVA.org:uu-344203" >
Efficacy and safety...
-
Ferolla, PieroUmbria Reg Canc Network, Multidisciplinary NET Grp, Dept Med Oncol, I-06126 Perugia, Italy.;Univ Perugia, Perugia, Italy.
(författare)
Efficacy and safety of long-acting pasireotide or everolimus alone or in combination in patients with advanced carcinoids of the lung and thymus (LUNA) : an open-label, multicentre, randomised, phase 2 trial
- Artikel/kapitelEngelska2017
Förlag, utgivningsår, omfång ...
Nummerbeteckningar
-
LIBRIS-ID:oai:DiVA.org:uu-344203
-
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-344203URI
-
https://doi.org/10.1016/S1470-2045(17)30681-2DOI
Kompletterande språkuppgifter
-
Språk:engelska
-
Sammanfattning på:engelska
Ingår i deldatabas
Klassifikation
-
Ämneskategori:ref swepub-contenttype
-
Ämneskategori:art swepub-publicationtype
Anmärkningar
-
BackgroundThere are no data from prospective studies focused exclusively on patients with advanced lung and thymic carcinoids. We aimed to assess the efficacy and safety of long-acting pasireotide and everolimus, administered alone or in combination, in patients with advanced carcinoids of the lung or thymus.MethodsLUNA was a prospective, multicentre, randomised, open-label, phase 2 trial of adult patients (aged >18 years) with advanced (unresectable or metastatic), well differentiated carcinoid tumours of the lung or thymus, with radiological progression within 12 months before randomisation, and a WHO performance status of 0–2. At each centre, the investigator or their designee registered each patient using an interactive voice recognition system into one of the three treatment groups. The randomisation allocation sequence was generated by an external company; patients were randomly assigned (1:1:1) to receive treatment with long-acting pasireotide (60 mg intramuscularly every 28 days), everolimus (10 mg orally once daily), or both in combination, for the core 12-month treatment period. Patients were stratified by carcinoid type (typical vs atypical) and line of study treatment (first line vs others). The primary endpoint was the proportion of patients progression-free at month 9, defined as the proportion of patients with overall lesion assessment at month 9 showing a complete response, partial response, or stable disease according to local Response Evaluation Criteria in Solid Tumors, version 1.1, assessed in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study drug and had at least one post-baseline safety assessment. The trial is registered with ClinicalTrials.gov, number NCT01563354. The extension phase of the study is ongoing.FindingsBetween Aug 16, 2013, and Sept 30, 2014, 124 patients were enrolled from 36 centres in nine countries: 41 were allocated to the long-acting pasireotide group, 42 to the everolimus group, and 41 to the combination group. At month 9, the proportion of patients with an overall lesion assessment of complete response, partial response, or stable disease was 16 of 41 patients (39·0%, 95% CI 24·2–55·5) in the long-acting pasireotide group, 14 of 42 patients (33·3%, 19·6–49·5) in the everolimus group, and 24 of 41 patients (58·5%, 42·1–73·7) in the combination group. The most common grade 1–2 adverse events with a suspected association with long-acting pasireotide monotherapy were diarrhoea (15 [37%] of 41), hyperglycaemia (17 [41%]), and weight loss (8 [20%]); those with a suspected association with everolimus monotherapy were stomatitis (26 [62%] of 42) and diarrhoea (16 [38%]); and those suspected to be associated with combination treatment were hyperglycaemia (27 [66%] of 41]), diarrhoea (19 [46%]), and asthenia (8 [20%]). The most common grade 3–4 adverse events with a suspected association with long-acting pasireotide monotherapy were γ-glutamyltransferase increased (four [10%] of 41 patients), diarrhoea (three [7%]), and hyperglycaemia (three [7%]); those for everolimus were hyperglycaemia (seven [17%] of 42 patients), stomatitis (four [10%]), and diarrhoea (three [7%]); those for combination treatment were hyperglycaemia (nine [22%] of 41 patients) and diarrhoea (four [10%]). 11 patients died during the core 12-month treatment phase or up to 56 days after the last study treatment exposure date: two (5%) of 41 in the long-acting pasireotide group, six (14%) of 42 in the everolimus group, and three (7%) of 41 in the combination group. No deaths were suspected to be related to long-acting pasireotide treatment. One death in the everolimus group (acute kidney injury associated with diarrhoea), and two deaths in the combination group (diarrhoea and urinary sepsis in one patient, and acute renal failure and respiratory failure in one patient) were suspected to be related to everolimus treatment. In the latter patient, acute renal failure was not suspected to be related to everolimus treatment, but respiratory failure was suspected to be related.InterpretationThe study met the primary endpoint in all three treatment groups. Safety profiles were consistent with the known safety profiles of these agents. Further studies are needed to confirm the antitumour efficacy of the combination of a somatostatin analogue with everolimus in lung and thymic carcinoids.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
-
Brizzi, Maria PiaSan Luigi Hosp, Dept Oncol, Orbassano, Italy.
(författare)
-
Meyer, TimRoyal Free Hosp, Dept Med Oncol, London, England.;UCL, London, England.
(författare)
-
Mansoor, WasatChristie NHS Fdn Trust, Dept Med Oncol, Manchester, Lancs, England.
(författare)
-
Mazieres, JulienUniv Paul Sabatier, CHU Toulouse, Pneumol, Toulouse, France.
(författare)
-
Do Cao, ChristineCHRU Lille, Med Oncol, Lille, France.
(författare)
-
Lena, HerveCtr Hosp Univ, Pneumol, Rennes, France.
(författare)
-
Berruti, AlfredoUniv Brescia, Med Oncol, Brescia, Italy.
(författare)
-
Damiano, VincenzoUniv Naples Federico II, Mol Canc Therapy, Naples, Italy.
(författare)
-
Buikhuisen, WienekeNetherlands Canc Inst, Dept Thorac Oncol, Amsterdam, Netherlands.
(författare)
-
Gronbaek, HenningAarhus Univ Hosp, Dept Hepatol & Gastroenterol, Aarhus, Denmark.
(författare)
-
Lombard-Bohas, CatherineHosp Civils Lyon, Dept Med Oncol, Lyon, France.
(författare)
-
Grohe, ChristianEvangel Lungenklin Berlin, Thorac Oncol, Berlin, Germany.
(författare)
-
Minotti, VincenzoOsped S Maria Misericordia, Dept Med Oncol, Perugia, Italy.
(författare)
-
Tiseo, MarcelloUniv Hosp Parma, Med Oncol, Parma, Italy.
(författare)
-
De Castro, JavierHosp La Paz Madrid, Oncol, Madrid, Spain.
(författare)
-
Reed, NicholasGartnavel Royal Hosp, Clin Oncol, Glasgow, Lanark, Scotland.
(författare)
-
Gislimberti, GabriellaNovartis Farma SpA, Origgio, Italy.
(författare)
-
Singh, NehaCognizant Technol Solut, Bombay, Maharashtra, India.
(författare)
-
Stankovic, MionaNovartis Pharma Serv Inc, Belgrade, Serbia.
(författare)
-
Öberg, Kjell,1946-Uppsala universitet,Endokrin tumörbiologi(Swepub:uu)kjellob
(författare)
-
Baudin, EricInst Gustave Roussy, Endocrine Oncol & Nucl Med, Villejuif, France.
(författare)
-
Umbria Reg Canc Network, Multidisciplinary NET Grp, Dept Med Oncol, I-06126 Perugia, Italy.;Univ Perugia, Perugia, Italy.San Luigi Hosp, Dept Oncol, Orbassano, Italy.
(creator_code:org_t)
Sammanhörande titlar
-
Ingår i:The Lancet Oncology18:12, s. 1652-16641470-20451474-5488
Internetlänk
Hitta via bibliotek
Till lärosätets databas
- Av författaren/redakt...
-
Ferolla, Piero
-
Brizzi, Maria Pi ...
-
Meyer, Tim
-
Mansoor, Wasat
-
Mazieres, Julien
-
Do Cao, Christin ...
-
visa fler...
-
Lena, Herve
-
Berruti, Alfredo
-
Damiano, Vincenz ...
-
Buikhuisen, Wien ...
-
Gronbaek, Hennin ...
-
Lombard-Bohas, C ...
-
Grohe, Christian
-
Minotti, Vincenz ...
-
Tiseo, Marcello
-
De Castro, Javie ...
-
Reed, Nicholas
-
Gislimberti, Gab ...
-
Singh, Neha
-
Stankovic, Miona
-
Öberg, Kjell, 19 ...
-
Baudin, Eric
-
visa färre...
- Om ämnet
-
- MEDICIN OCH HÄLSOVETENSKAP
-
MEDICIN OCH HÄLS ...
-
och Klinisk medicin
-
och Cancer och onkol ...
- Artiklar i publikationen
-
The Lancet Oncol ...
- Av lärosätet
-
Uppsala universitet